Erythromycin and its derivatives are known to have motilin agonistic actions, among which accelerating gastric emptying is considered as a typical action (Janssens, Peeters et al. 1990). Gastroparesis is a symptom in the digestive tract that manifests itself in association with diabetes mellitus and the like; conventionally, it is considered a symptom that occurs from delayed gastric emptying and in Japan, the identification of delayed gastric emptying is employed to make definitive diagnosis of gastroparesis.
An idea of treating patients with delayed gastric emptying by accelerating gastric emptying using motilin agonists was put forth and the drugs were shown to accelerate gastric emptying in clinical settings (Maganti, Onyemere et al. 2003; Russo, Stevens et al 2004). It was shown that such delay of gastric emptying correlated with the motility of the digestive tract evaluated on an electrogastrogram (Cucchiara, Franzese et al. 1998). However, since the primary objective of treating gastroparesis is to improve gastroparesis symptom in the epigastrium, restoring gastric emptying is not the final goal of the treatment. In addition, it turned out that the delaying of gastric emptying did not commonly correlate with gastroparesis symptom (De Block, De Leeuw et al. 2002) and that many of the patients who presented with gastroparesis symptom did not show delayed gastric emptying (Kong, Horowitz et al. 1999), making it no longer rationale to adopt the strategy of achieving a symptomatic improvement through the acceleration of gastric emptying. Improving the gastroparesis symptom in patients having symptomatic gastroparesis is currently considered the most important objective in therapy and there is a need to provide therapeutic drugs that can improve the gastroparesis symptom in the patients.
Further, in a study of 383 patients with gastroparesis using the erythromycin derivative ABT-229 which had been shown clinically to be capable of accelerating gastric emptying, no efficacy in the patients with both delayed gastric emptying and non-delayed gastric emptying was reported, showing that accelerating gastric emptying was not relevant with the improvement in gastroparesis symptom (Talley, Verlinden et al. 2001). For ABT-229, a discovery may be found in J. Med. Chem. 2004, Vol. 47, pp. 1704-1708.

Under these situations, it is required in the treatment of gastroparesis to develop pharmaceuticals that not only accelerate the motility of the gastrointestinal tract such as gastric emptying but also improve the gastroparesis symptom. As of today, no drugs have ever been succeeded for the development that were demonstrated to improve gastroparesis symptom (Talley 2003) and the patients having gastroparesis are in need of therapeutic and/or preventive drugs for improving the gastroparesis symptom that enable them to perceive an improvement in the symptom and which can be administered over an extended period of time with sustained improvement in the symptom.
Speaking now of JP 6-56843 A and WO93/24509, these references mention that specific compounds of erythromycin derivatives have motilin-agonistic actions as well as the ability to enhance the motility of the upper digestive tract. Moreover, 8,9-didehydro-N-demethyl-9-deoxo-6,11-dideoxy-6,9-epoxy-12-O-methyl-N-(1-methylethyl)-11-oxoerythromycin which is one of those typical compounds has been reported to have a much weaker antibacterial action than erythromycin, suggesting the potential of its long-term clinical use (Koga, Sato et al. 1994). Further, those compounds have been shown to accelerate gastric emptying in a clinical study (Fang, McCallum et al. 2001). However, it is not known whether those compounds, unlike the aforementioned erythromycin derivative ABT-229, are capable of improving gastroparesis symptom. Hence, as already mentioned above, there is a need to provide therapeutic and/or preventive agents against gastroparesis symptom that is capable for continuous medication.